AEŠH metodes izstrāde radniecisku piemaisījumu noteikšanai Ivabradīna paraugos

Abstract

AEŠH metodes izstr􀆗de radniecisku piemais􀆯jumu noteikšanai Ivabrad􀆯na paraugos. Sitčihins V., zin􀆗tniskais vad􀆯t􀆗js Dr. 􀆷􀆯m., Nakurte I. Ma􀆧istra darbs, 50 lappuses, 35 att􀆝li, 12 tabulas, 15 literat􀇌ras avoti, 2 pielikumi. Latviešu valod􀆗. Darba ietvaros analiz􀆝ts Ivabrad􀆯ns un 7 t􀆗 zin􀆗mie radnieciskie piemais􀆯jumi, izv􀆝l􀆝ta savienojumu atdal􀆯šanas un detekt􀆝šanas metode. Darba gait􀆗 noteiktas katra individu􀆗l􀆗 savienojuma detekt􀆝šanas robežas un linearit􀆗tes apgabals. P􀆗rbaud􀆯ta Ivabrad􀆯na stabilit􀆗te stresa test􀆝šanas apst􀆗kļos, izmantojot masspektrometrisko (MS) detekt􀆝šanu noteiktas dažu degrad􀆗cijas produktu molekul􀆗ro jonu m/z v􀆝rt􀆯bas. Divu hidrol􀆯zes produktu strukt􀇌ras ir identific􀆝tas, balstoties uz literat􀇌ras datiem. Darba rezult􀆗t􀆗 izstr􀆗d􀆗ta AEŠH metode, kuru var izmantot tand􀆝m􀆗 ar MS detekt􀆝šanu. Metode ļauj selekt􀆯vi noteikt hidrol􀆯zes, termol􀆯zes un sint􀆝zes blakusproduktu saturu Ivabrad􀆯na paraugos. P􀆗rbaud􀆯ja metodes atbilst􀆯bu EF jut􀆯bas, ticam􀆯bas, atk􀆗rtojam􀆯bas un robustuma prasībām validācijas testu ietvaros. Visi testi bija veikti saska􀆼􀆗 ar ICH vadl􀆯nij􀆗m.Development of an HPLC Method for Estimation of Related Substances in Ivabradine. Sitcihins V., supervisor Dr. chem. Nakurte I. Master thesis, 50 pages, 35 figures, 12 charts, 15 literature references, 2 appendices. In Latvian. This thesis documents the development of an HPLC analytical method for detection of synthesis by-products and other related substances in Ivabradine. A sensitive detection method has been selected according to the analytes' structures and properties. Optimal chromatographic separation conditions have been experimentally determined. The thesis features a study of Ivabradine's stability and degradation. Basic and acidic hydrolysis, oxidation, thermolysis, as well as photolysis tests have been performed on Ivabradine. Mass spectra of some of the detected degradation products have been obtained. Two hydrolysis products have been identified, and their proposed structures have been found based on a scientific publication. MS-compatible HPLC analytical method has been developed for specific detection of 2 hydrolysis products, 2 thermolysis products and 7 known impurities in Ivabradine. The LOD's and the linearity ranges have been determined for each known substance. Tests of the method's compliance with the EP requirements of sensitivity, accuracy, repeatability and robustness have been executed. All the validation tests have been performed according to ICH guidelines.